Obesity is the most common nutritional disorder in industrialized countries. US statistics show that more than one third of U.S. adults and 20% of U.S. children are obese, and more than 70% of patients with type II diabetes are obese. Obesity is also a major risk factor for the development of hypertension, hyperlipidemia and some types of cancer. It has been known that obesity is particularly prevalent in patients with carbohydrate metabolism disorders and non-insulin-dependent diabetes mellitus, and weight gain exacerbates the diabetic condition, but the causal nature between diabetes and obesity remains unclear. Not all patients with extremely severe obesity will have diabetes, and obesity alone is not sufficient to cause non-insulin-dependent diabetes mellitus, and either genetic or environmental factors are recognized to be involved in its onset. However, the incidence of non-insulin-dependent diabetes mellitus is much higher in obese people, and also closely related to the degree and duration of obesity. Thus, obesity is a major risk factor for non-insulin-dependent diabetes mellitus.
Meanwhile, body fat distribution as well as degree of obesity has been recently reported to be closely related to obesity-related disorders. Abdominal obesity, in particular, is a growing public health problem.
Patients with non-insulin-dependent diabetes mellitus commonly have obesity or a previous history of obesity. It was reported that 60˜90% of Western people with non-insulin-dependent diabetes mellitus are obese and about 70% of Korean patients with non-insulin-dependent diabetes mellitus have a previous history of obesity (Joong-Yeol Park et al., Body Weight Changes of Non-Insulin Dependent Diabetic Patients in Korea, Diabetes, 17, pp. 51-57, 1993).
Many prospective studies revealed that obesity precedes the development of impaired glucose tolerance and non-insulin-dependent diabetes mellitus (Carey V J. et al., Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women, The nurses' health study, Am J Epidemiol, 145, pp. 614-619, 1997). The Framingham study demonstrated that impaired glucose tolerance is frequently observed in obese people, and most studies showed that obese people with impaired glucose tolerance are at a high risk for developing non-insulin-dependent diabetes mellitus.
A mechanism for the development of diabetes from obesity has not been clarified yet, but increased insulin resistance is regarded as a key factor. Felber et al., on the basis of the epidemiological evidence, divided obese people into four groups (normal glucose tolerance, impaired glucose tolerance, hyperinsulinemic diabetes, and hypoinsulinemic diabetes groups), depending on glucose and insulin responses after an oral glucose tolerance test, and they suggested that this process is involved in the development of diabetes from obesity (Golay A. et al., Obesity and NIDDMP, the retrograde regulation concept, Diabetes Rev, 5, pp. 69-82, 1997).
Carbohydrate metabolism in obesity shows insulin resistance, which is defined as normal glucose level and elevated insulin level in response to the oral glucose tolerance test. Insulin resistance is a central pathological defect found in obesity patients and obese patients with non-insulin-dependent diabetes mellitus, and is observed in the early stages of obesity. There have been many hypotheses on the mechanism concerning the reduced insulin action in obesity, but it is not clarified yet. That is, functional reduction of insulin receptors involved in insulin action, glucose receptors, and enzymes involved in glucose synthesis and glucose oxidation is observed in the obese, which is understood as a secondary phenomenon due to obesity (Golay A. et al., Obesity and NIDDMP, the retrograde regulation concept, Diabetes Rev, 5, pp. 69-82, 1997).
Some circumstantial evidence suggests that adipocyte plays a central role in the development of the insulin resistance. That is, several adipocyte-secreted factors or metabolic messengers are considered to impair insulin action in the muscle and liver. A first, widely recognized factor is extracellular free fatty acids generated by the hydrolysis of storage triglyceride in the adipose tissue. In addition, TNF-α and leptin secreted by adipose tissue are recently suggested to cause insulin resistance in obesity (Hotamisligil G S. et al., Tumor necrosis factor a, a key component of the obesity-diabetes link, Diabetes, 43, pp. 1271-1278, 1994).
Energy metabolism in obesity tends to increase both degradation and synthesis of lipids. Obesity, in particular, abdominal obesity, is characterized by an increase in lipid degradation and free fatty acid availability. Reportedly, there is a strong correlation between body fat mass and fat oxidation, suggesting that the increased blood free fatty acid level and lipid oxidation are attributed to the increase in fat mass. Increased lipid oxidation is observed even in the early stages of obesity, and also on an empty stomach or after a glucose load.
In Korea, the number of obese people is dramatically increasing because of the improved living standard and Westernized eating habits. Obesity causes or worsens many diseases including hypertension, arteriosclerosis, fatty liver, and diabetes. Therefore, prevention of obesity is important, and when obesity occurs, it is necessary to activate the body metabolism through reduction of body fat and improvement of lipid metabolism for health promotion and disease prevention.
Anemarrhena asphodeloides Bunge (called Ji-mo in Korea), is a perennial herb belonging to the family Liliaceae, and the dried root-like stem of Anemarrhena asphodeloides Bunge is used in traditional medicine. Anemarrhena asphodeloides Bunge is native to northern China, and widely grows in Korea (Hwang Hae and Pyong-nam Province), China, Mongolia and the region. Since the rhizome looks like a bug, it is called Ji-mo in Korea, a play on words in the Korean language. It has a distinctive odor, and is slightly bitter and sweet in taste, and viscous when chewed. It has diuretic, antipyretic, and antitussive effects.
Anemarrhena asphodeloides Bunge was known to contain about 6% steroid saponin, timosaponin A-I, A-II, A-III, and A-IV (water-insoluble part of methyl alcohol X), timosaponin B-I and B-II (water-soluble part), sarsasapogenin, markogenin, and neogitogenin as saponin, xanthone; mangiferin, isomangiferin, and 200 μg/g of nicotinic acid as vitamin (Park Jong-Hee, the encyclopedia of Chinese crude drugs (Vol. 2), Sinil Sangsa, pp. 746-748, 2002), but there is no previous mention that an extract of Anemarrhena asphodeloides Bunge or compounds isolated from the same improve lipid metabolism.